Effect of Sotagliflozin on Early Mortality and Heart Failure-Related Events: A Post Hoc Analysis of SOLOIST-WHF

Bertram Pitt; Deepak L Bhatt; Michael Szarek; Christopher P Cannon; Lawrence A Leiter; Darren K McGuire; Julia B Lewis; Matthew C Riddle; Adriaan A Voors; Marco Metra; Lars H Lund; Michel Komajda; Jeffrey M Testani; Christopher S Wilcox; Piotr Ponikowski; Renato D Lopes; Justin A Ezekowitz; Franklin Sun; Michael J Davies; Subodh Verma; Mikhail N Kosiborod; Ph Gabriel Steg; SOLOIST-WHF Investigators

doi:10.1016/j.jchf.2023.05.026

Effect of Sotagliflozin on Early Mortality and Heart Failure-Related Events: A Post Hoc Analysis of SOLOIST-WHF

JACC Heart Fail. 2023 Aug;11(8 Pt 1):879-889. doi: 10.1016/j.jchf.2023.05.026.

Authors

Bertram Pitt¹, Deepak L Bhatt², Michael Szarek³, Christopher P Cannon⁴, Lawrence A Leiter⁵, Darren K McGuire⁶, Julia B Lewis⁷, Matthew C Riddle⁸, Adriaan A Voors⁹, Marco Metra¹⁰, Lars H Lund¹¹, Michel Komajda¹², Jeffrey M Testani¹³, Christopher S Wilcox¹⁴, Piotr Ponikowski¹⁵, Renato D Lopes¹⁶, Justin A Ezekowitz¹⁷, Franklin Sun¹⁸, Michael J Davies¹⁹, Subodh Verma⁵, Mikhail N Kosiborod¹⁹, Ph Gabriel Steg²⁰; SOLOIST-WHF Investigators

Affiliations

¹ Department of Internal Medicine (Emeritus), University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
² Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: DLBhattMD@post.Harvard.edu.
³ School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, New York, USA; University of Colorado School of Medicine, Aurora, CO, USA; CPC Clinical Research, Aurora, Colorado, USA.
⁴ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁵ Li Ka Shing Knowledge Institute, St. Michael's Hospital, and University of Toronto, Toronto, Ontario, Canada.
⁶ University of Texas Southwestern Medical Center, and Parkland Health and Hospital System, Dallas, Texas, USA.
⁷ Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁸ Oregon Health & Science University, Portland, Oregon, USA.
⁹ University of Groningen-University Medical Center Groningen, Groningen, the Netherlands.
¹⁰ Azienda Socio Sanitaria Territoriale Spedali Civili and University of Brescia, Brescia, Italy.
¹¹ Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
¹² Paris Sorbonne University and Groupe Hospitalier Paris Saint Joseph, Paris, France.
¹³ Yale University, New Haven, Connecticut, USA.
¹⁴ Georgetown University, Washington, DC, USA.
¹⁵ Wroclaw Medical University, Wroclaw, Poland.
¹⁶ Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁷ University of Alberta and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada.
¹⁸ Lexicon Pharmaceuticals Inc., The Woodlands, Texas, USA.
¹⁹ Department of Cardiovascular Medicine, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.
²⁰ Université Paris-Cité, Institut Universitaire de France, INSERM U-1148, FACT (French Alliance for Cardiovascular Trials) and AP-HP (Assistance Publique-Hôpitaux de Paris), Hopital Bichat Paris, Paris, France.

PMID: 37558385
DOI: 10.1016/j.jchf.2023.05.026

Abstract

Background: Approximately 25% of patients admitted to hospitals for worsening heart failure (WHF) are readmitted within 30 days.

Objectives: The authors conducted a post hoc analysis of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post-WHF) trial to evaluate the efficacy of sotagliflozin versus placebo to decrease mortality and HF-related events among patients who began study treatment on or before discharge from their index hospitalization.

Methods: The main endpoint of interest was cardiovascular death or HF-related event (HF hospitalization or urgent care visit) occurring within 90 and 30 days after discharge for the index WHF hospitalization. Treatment comparisons were by proportional hazards models, generating HRs, 95% CIs, and P values.

Results: Of 1,222 randomized patients, 596 received study drug on or before their date of discharge. Sotagliflozin reduced the main endpoint at 90 days after discharge (HR: 0.54 [95% CI: 0.35-0.82]; P = 0.004) and at 30 days (HR: 0.49 [95% CI: 0.27-0.91]; P = 0.023) and all-cause mortality at 90 days (HR: 0.39 [95% CI: 0.17-0.88]; P = 0.024). In subgroup analyses, sotagliflozin reduced the 90-day main endpoint regardless of sex, age, estimated glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, left ventricular ejection fraction, or mineralocorticoid receptor agonist use. Sotagliflozin was well-tolerated but with slightly higher rates of diarrhea and volume-related events than placebo.

Conclusions: Starting sotagliflozin before discharge in patients with type 2 diabetes hospitalized for WHF significantly decreased cardiovascular deaths and HF events through 30 and 90 days after discharge, emphasizing the importance of beginning sodium glucose cotransporter treatment before discharge.

Keywords: SGLT2 inhibitor; dual SGLT1 and SGLT2 inhibitor; heart failure-related events; hospital readmission; mortality; sotagliflozin.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Heart Failure*
Hospitalization
Humans
Stroke Volume
Ventricular Function, Left

Substances

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol